For operations in the fields of oral surgery and dental treatment, in particular, for tooth extraction and the like in the field of dental treatment, anesthetics for local injection (agents for local anesthesia) containing lidocaine (2-diethylamino-N-(2,6-dimethyl-phenyl)acetamide) as an active ingredient have been used. For example, “Xylocaine Cartridge for Dental Use” (Fujisawa Pharmaceutical Co., Ltd.) has been clinically used. This agent for local anesthesia is a composition for topical administration which contains 20 mg of lidocaine hydrochloride and 0.0125 mg of epinephrine per 1 ml of a solution for injection. The agent is generally used in an amount of 0.3-1.8 ml to carry out infiltration anesthesia or block anesthesia (see, a package insert of the drug).
Agents for local anesthesia are generally formulated with a catecholamine such as epinephrine which has angiotonic effect on local capillary blood vessels to reduce blood flow. The effect of the catecholamine is to decrease bleeding in a field of operation by lowering blood flow, and to reduce transmigration (diffusion) of an anesthetic agent being an active ingredient into blood and maintain high concentration of the anesthetic agent in the local tissue to achieve a prolonged local anesthetic effect (Collins, V. J., Principles of Anesthesiology, 2nd Ed., Lea and Febiger, Philadelphia, 1976; as a review about agents for dental local anesthesia, see, Dental Outlook, special edition, “Medical practice of tooth extraction,” 4. Dental local anesthetics, pp. 84-94, 1979).
However, because epinephrine contained in topically administered anesthetics may possibly cause vasoconstriction in other tissues or in the whole body, it has been so far pointed out that local anesthetics containing epinephrine have possibilities of danger for administration to patients with hypertonia, anteriosclerosis, cardiac failure, hyperthyreosis, or diabetes or a patient who has experienced angiospasm. Therefore, the administration of the drug is a contraindication in principle (The term “contraindication in principle” means that an administration to the above patients is not allowed in principle, and when an administration is particularly required the administration needs to be performed very carefully: Announcement in June, 2000, by Chief of safety measure Division of Pharmaceutical and Medical Safety Bureau of Ministry of Health and Welfare).
In dental lidocaine preparations which are clinically used, epinephrine is mixed at 1/80,000 (g/ml, 0.0125 mg per ml). For the purpose of decreasing side effects of epinephrine, anesthetics for dental use containing about 1/200,000 (g/ml) of epinephrine (0.005 mg as a free base per ml) are proposed as compositions for local anesthesia having durability suitable for short-time dental operations such as tooth extraction (WO 97/07794). By using said anesthetics, necessary and sufficient durability of anesthetic action for minor dental operations and the like can be achieved, however, the possibility of side effects of epinephrine can not be completely eliminated. Therefore, other means for maintaining the action of local anesthetics are desired to be provided.